Cilostazol as an alternative to aspirin after ischaemic stroke: a randomised, double-blind, pilot study
Cilostazol as an alternative to aspirin after ischaemic stroke: a randomised, double-blind, pilot study
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DOI：
10.1016/s1474-4422(08)70094-2
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发表时间：
2008-06-01
期刊：
影响因子：
48
通讯作者：
Yao, Chen
中科院分区：
文献类型：
--
作者：
Huang, Yining;Cheng, Yan;Yao, Chen
背景大多数中风患者服用阿司匹林;然而，阿司匹林相关的脑出血是目前令人担忧的并发症，特别是在中国，二级预防计划和社区内脑出血的发病率很高。西洛他唑是一种磷酸二酯酶3（PDE 3）抑制剂，是阿司匹林的替代品，通过不同的机制发挥作用。本试验的目的是比较西洛他唑与阿司匹林的长期预防缺血性stroke.Methods复发的疗效和安全性，720例患者（平均年龄60.2岁，SD 9.86）谁曾在过去的1-6个月内缺血性中风连续入组的前瞻性，多中心，双盲，随机试验。360名患者被随机分配接受西洛他唑治疗，360名患者接受阿司匹林治疗。采用意向治疗分析，两组患者均服药12-18个月。主要终点为试验期间卒中复发（缺血性卒中、出血性卒中或蛛网膜下腔出血）。在研究开始和结束时，所有患者均进行MRI，包括T1 MRI、T2 MRI、弥散加权成像（DWI）、T2液体衰减反转恢复（FLAIR）和T2梯度回波成像（T2*）。该试验注册于ClinicalTrials.gov，编号NCT 00202020。结果平均治疗持续时间为740人年，分析了719例患者（西洛他唑组360例，阿司匹林组359例）。西洛他唑组12例患者和阿司匹林组20例患者报告了主要终点。使用Kaplan-Meier曲线计算的估计风险比（西洛他唑组与阿司匹林组的主要终点风险）为0.62（95% CI 0.30-1.26; p=0.185）。6例患者报告了症状性脑出血：西洛他唑组1例，阿司匹林组5例。阿司匹林组4例患者和西洛他唑组1例患者出现无症状脑血肿。脑出血事件在阿司匹林组比西洛他唑组明显更常见（7 vs 1，p=0.034）。所有的6名患者有症状的出血有以前的脑微出血在该地区的血肿location.Interpretation-本试点研究的结果显示，缺血性中风患者之间的复发率没有显着差异，随机分配到服用西洛他唑或阿司匹林。西洛他唑组缺血性和出血性卒中的发生率较低，表明西洛他唑可能是中国缺血性卒中患者中阿司匹林的更有效和更安全的替代药物;然而，需要更大规模的III期试验来证实这一点。
Background Most patients who have had a stroke are given aspirin; however, aspirin-related cerebral haemorrhage is a complication that is currently of concern, particularly in China where there is a high incidence of cerebral haemorrhage in secondary prevention programmes and within the community. Cilostazol, a phosphodiesterase 3 (PDE3) inhibitor, is an alternative to aspirin that works through a different mechanism. This trial aimed to compare the efficacy and safety of cilostazol with that of aspirin for the long-term prevention of the recurrence of ischaemic stroke.Methods 720 patients (mean age 60.2 years, SD 9.86) who had had an ischaemic stroke within the previous 1-6 months were enrolled consecutively in a prospective, multicentre, double-blind, randomised trial. 360 patients were randomly assigned to receive cilostazol and 360 patients to receive aspirin. Analysis was by intention to treat. Patients in both groups took the medication for 12-18 months. The primary endpoint was any recurrence of stroke (ischaemic stroke, haemorrhagic stroke, or subarachnoid haemorrhage) during the trial period. All patients had MRI with T1 MRI, T2 MRI, diffusion-weighted imaging (DWI), T2 fluid-attenuated inversion recovery (FLAIR), and T2 gradient echo imaging (T2*) at the beginning and the end of the study. This trial is registered with ClinicalTrials.gov, number NCT00202020.Findings The average duration of treatment was 740 person-years, and 719 patients were analysed (360 in the cilostazol group and 359 in the aspirin group). The primary endpoint was reported in 12 patients in the cilostazol group and in 20 patients in the aspirin group. The estimated hazard ratio, calculated with Kaplan-Meier curves (risk of primary endpoint in cilostazol group vs aspirin group), was 0.62 (95% CI 0.30-1.26; p=0.185). Symptomatic cerebral haemorrhage was reported in six patients: one in the cilostazol group and five in the aspirin group. Asymptomatic cerebral haematoma was found in four patients in the aspirin group and one patient in the cilostazol group. Brain bleeding events were significantly more common in the aspirin group than in the cilostazol group (7 vs 1, p=0.034). All of the six patients with symptomatic haemorrhage had previous cerebral microbleeds in the area where the haematoma was located.Interpretation The results of this pilot study showed no significant difference in the rate of recurrence of stroke between patients with ischaemic stroke who were randomly assigned to take either cilostazol or aspirin. The lower rates of ischaemic and haemorrhagic stroke in the cilostazol group suggest that cilostazol might be a more effective and safer alternative to aspirin for Chinese patients with ischaemic stroke; however, a larger phase III trial is required to confirm this.